PROJECT SUMMARY/ABSTRACT Supplement Title: Analyzing the complex genetics of late-onset Alzheimer's disease in human and mouse models We propose to supplement an existing R01 award, Methods and Tools to Analyze Genetic Complexity (R01GM115518), to analyze genetic networks that influence transcriptional patterns relevant to late-onset Alzheimer's disease (LOAD). This analysis will accelerate the creation of new mouse models of LOAD by identifying genetic loci that interactively modify transcriptomes in a way that mimics analogous human signatures derived from postmortem brain samples. We will use the broad library of LOAD-related gene expression changes from a recent meta-analysis from the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD). Genetic factors identified will be used as candidate factors in the Model Organism Development and Evaluation for Late-onset Alzheimer's Disease (MODEL-AD) Consortium. This supplemental project will therefore harness the pilot award methods to address the complex genetics of LOAD, drawing from and feeding into existing NIA-funded consortia.